Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Lung Cancer. 2018 Feb;116:90-95. doi: 10.1016/j.lungcan.2018.01.002. Epub 2018 Jan 4.
Although a growing list of essential genomic/immune-based biomarkers are linked to approved non-small-cell lung cancer (NSCLC) therapies worldwide, few reports have detailed the evolution of NSCLC predictive biomarker assessment in routine clinical practice.
We retrospectively reviewed the first one thousand plus NSCLC patient specimens from our institution analyzed for predictive biomarkers from 2004 to 2017 and evaluated patterns of testing as well as correlation with clinical-pathologic characteristics.
The majority of 1009 NSCLC patients had advanced stages of adenocarcinoma with most tissues obtained from the lung, mediastinal/hilar nodes, or pleura. The majority of testing was performed on cytology or small biopsy specimens. All were tested for EGFR mutations, 895 for ALK rearrangement, 841 for KRAS mutation, 537 for ROS1 rearrangement, and 179 using comprehensive genomic profiling. Implementation of near-universal genomic biomarker testing at our institution for EGFR, ALK, ROS1 and PD-L1 all occurred within the first year following evidence of clinical activity or regulatory body approval of an associated inhibitor. The overall testing failure rate after use of the best specimen for the most common tests was ≤5.5%. A quarter of tumors had a driver oncogene identified (EGFR/ALK/ROS1/BRAF V600E) with an approved oral targeted therapy, with the highest prevalence in those patients with no or light (≤15 pack-years) history of tobacco use.
Tumor biomarker testing using clinical NSCLC specimens in routine oncologic care evolves rapidly following approval of targeted therapies linked to diagnostic assays. Our practice's decade plus experience highlights the rapid evolution of biomarker testing and confirms the therapeutic relevance of such testing in all patients-particularly those patients with light/no history of tobacco use.
尽管越来越多与已批准的非小细胞肺癌（NSCLC）治疗相关的基因组/免疫基础生物标志物被列入其中，但很少有报道详细描述 NSCLC 预测性生物标志物评估在常规临床实践中的演变。
我们回顾性分析了 2004 年至 2017 年我院 1000 多例 NSCLC 患者的标本，这些标本用于分析预测性生物标志物，并评估了检测模式以及与临床病理特征的相关性。
1009 例 NSCLC 患者中，大多数为腺癌晚期，大部分组织取自肺部、纵隔/肺门淋巴结或胸膜。大多数检测是针对细胞学或小活检标本进行的。所有患者均检测 EGFR 突变，895 例检测 ALK 重排，841 例检测 KRAS 突变，537 例检测 ROS1 重排，179 例进行全面基因组分析。在我们医院，EGFR、ALK、ROS1 和 PD-L1 的近全基因组生物标志物检测的实施，均发生在相关抑制剂的临床活性或监管机构批准后的第一年。最常见检测中，使用最佳标本的总体检测失败率≤5.5%。四分之一的肿瘤发现了驱动致癌基因（EGFR/ALK/ROS1/BRAF V600E），并存在一种获批的口服靶向治疗药物，在那些无或轻度（≤15 包年）吸烟史的患者中，这种情况最为常见。
在与诊断检测相关的靶向治疗药物获得批准后，使用临床 NSCLC 标本进行肿瘤生物标志物检测在常规肿瘤治疗中迅速发展。我们的十年以上经验突出了生物标志物检测的快速演变，并证实了此类检测在所有患者中的治疗相关性，尤其是那些无或轻度吸烟史的患者。
